Project Summary/Abstract Asthma is a lung disease that is growing in prevalence and disproportionately affects children. Many asthmatics show underlying allergic inflammation that is thought to trigger their symptoms, and suppressing inflammation shows efficacy in treating disease. However, the mechanism by which allergen inhaled into the lung actually initiates inflammatory responses is poorly understood. In particular, the allergen must be taken up by so-called professional antigen presenting cells to be presented to CD4 T cells, yet the uptake of allergen from the airway lumen has not been well characterized. In preliminary studies, we have identified a subset of macrophages which appear to be the main allergen capturing cells near the bronchi, where inflammation develops. These bronchus-associated macrophages are phenotypically distinct from alveolar macrophages in the distal airways as well as from classical dendritic cells. The overall goal of this proposal is to determine whether bronchus-associated macrophages are important for the allergic inflammation near the bronchial tree. The specific aims are to 1) characterize the distinct features and cellular interactions of bronchus-associated macrophages compared with classical dendritic cells and 2) assess the impact of deficiency in bronchus- associated macrophages on allergic lung inflammation. We believe these studies will provide important new insights into the mechanism by which allergen is taken up from the bronchi in the initiation of allergic lung inflammation, which may have important implications for understanding the pathogenesis of asthma.